The goal of this proposal is: To provide the scientific community with an unprecedented amount of assembled high-quality genome sequence, sufficient in quantity and quality to solve some of the central intellectual questions in genomics. In particular, the genome sequence will allow comparative studies to identify the vast majority of functional elements encoded in the human genome. It will also allow extensive characterization of the biological diversity in the animal and fungal kingdoms. We propose to do this, over a three-year period, by producing: Shotgun sequence: approximately 331 million reads yielding, approximately 205 Gb of high-quality raw bases, and approximately 32 Gb of high-quality draft genome assembly; Polished sequence: approximately 10 Gb; and Finished sequence: approximately 1.5 Gb. We also plan to aggressively improve the efficiency of the genome sequencing process. The cost of high quality draft sequence of a typical mammalian genome (about 2.7 Gb) will be approximately $25M in Year 1 and decrease to about $16M by Year 3.